The effect of acidic residues and amphipathicity on the lytic activities of mastoparan peptides studied by fluorescence and CD spectroscopy

Abstract

Some mastoparan peptides extracted from social wasps display antimicrobial activity and some are hemolytic and cytotoxic. Although the cell specificity of these peptides is complex and poorly understood, it is believed that their net charges and their hydrophobicity contribute to modulate their biological activities. We report a study, using fluorescence and circular dichroism spectroscopies, evaluating the influence of these two parameters on the lytic activities of five mastoparans in zwitterionic and anionic phospholipid vesicles. Four of these peptides, extracted from the venom of the social wasp Polybia paulista, present both acidic and basic residues with net charges ranging from +1 to +3 which were compared to Mastoparan-X with three basic residues and net charge +4. Previous studies revealed that these peptides have moderate-to-strong antibacterial activity against Gram-positive and Gram-negative microorganisms and some of them are hemolytic. Their affinity and lytic activity in zwitterionic vesicles decrease with the net electrical charges and the dose response curves are more cooperative for the less charged peptides. Higher charged peptides display higher affinity and lytic activity in anionic vesicles. The present study shows that the acidic residues play an important role in modulating the peptides' lytic and biological activities and influence differently when the peptide is hydrophobic or when the acidic residue is in a hydrophilic peptide.

Peptides as toxins/defensins

“…This issue is intended to present snapshots of the peptides identified as toxins/ defensins and to explore the diversity of biological systems, novel structures, and the mechanisms of action. The reviews and original manuscripts in this issue focus on peptides from insects Leite et al 2010), spiders Rodríguez et al 2010;Santos et al 2010), amphibians Libério et al 2010;Meneses et al 2010), and humans (Corrales-Garcia et al 2010) by using spectroscopic strategies for the detection, structural elucidation De Souza et al 2010;Leite et al 2010), and characterization of the molecular interactions with biological membranes Zhou et al 2010). Some of the contributions focus on the studies of the structure-activity relationship to achieve a better understanding of the mechanisms of the action .…”

Lipid-packing perturbation of model membranes by pH-responsive antimicrobial peptides

“…The substitution of aspartic acid (Asp) by an asparagine residue increases its net charge to +3. The increase in the net charge improved the leakage efficiency in anionic mixed LUVs and GUVs (Dos Santos Cabrera et al 2011;Leite et al 2011). The net charge of peptides concomitantly containing acidic and basic residues, Asp and Lys like MP1 and L1A, can be modulated by changes in the pH of the solution.…”

Prediction of improved antimicrobial mastoparan derivatives by 3D-QSAR-CoMSIA/CoMFA and computational mutagenesis

“…Results showed that Polybia-MP-1 is highly selective for bacterial cells; its lytic activity is characterized by a threshold peptide-to-lipid molar ratio that depends on the phospholipid composition of the vesicles. The same studies suggest that mastoparan analogs accumulate on the bilayer surface and induce a transient interruption to its barrier properties, leaking the vesicle contents [24][25][26].…”

“…Considering the wide therapeutic applicability of the mastoparans and extremely reduced number of side effects [21][22][23][24][25][26], the design and synthesis of new mastoparan derivatives appear to be a necessity in preclinical and clinical studies. On the other hand, limited knowledge about the mastoparan mechanism of action at the pathogen membranes requires application of methods by which the antimicrobial activity of new derivatives of mastoparan can be calculated without requiring the presence of microbial membranes.…”

“…Mastoparan is isolated from the venom of various wasp species: INLKALAALAKALL from wasps, INLKALA-ALAKKIL from vespula, VDWKKIGQHILSVL from Polistes jadwagae, or IDWKKLLDAAKQIL extracts from the social wasp Polybia paulista [21][22][23][24][25][26]. The mechanism of action of mastoparan variants (namely Polybia-MP-1, N2-Polybia-MP-1, and Mastoparan X) at the pathogen cellular level was studied in detail [11][12][13] by molecular dynamics simulations, circular dichroism, or fluorescence spectra.…”